Studies are being directed toward understanding the major histocompatibility complex, the structure and function of the products of this complex, and manipulations of immune responses to these products. Current studies include: 1) Characterization of major histocompatibility antigens: Congenic resistant strains, of mice developed, maintained, and used in serologic and immunochemical analyses of the MHC products of the mouse; 2) Studies of monoclonal antibodies to H-2 and la antigens: Hybridoma cell lines are produced by fusion of immune mouse spleen cells with mouse myeloma cells. The monoclonal anti-H-2 and anti-la antibodies produced by these hybridomas are analyzed by serologic and immunochemical means and are used to further characterize the fine structure of the MHC; 3) Mechanism of tolerance to H-2 and Ia antigens: The humoral and cellular responses of radiation bone marrow chimeras are examined, and the mechanism for maintenance of tolerance in these animals is studied; 4) Mixed allogeneic and xenogeneic chimeras: Irradiated animals are reconstituted with mixtures of T-cell depleted donor and host marrow, and the mechanism of tolerance and of immune responsiveness in these animals is studied in vivo and in vitro; 5) Non-lethal preparative regimens for bone marrow transplantation: Attempts to replace lethal irradiation with monoclonal antibody treatment in vivo are examined, and the immune status of the resulting animals is studied; and 6) Graft-vs-leukemia (GVL) effects of mixed bone marrow reconstitution: The effects of reconstitution with T-cell depleted syngeneic plus non-T-cell depleted allogeneic bone marrow on syngeneic leukemia are examined. Addition of IL-2 to the bone marrow reconstitution regimen for the first few days after transplantation has been found to have a marked anti GVHD effect. This project will terminate as of June 30, 1991.